tbuckley/cabot-search huggingface dataset:
Reliability of cancer registry primary payer information and implications for policy research.
Authors: Amy J. Davidoff, Lindsey Enewold, Courtney Williams, Manami Bhattacharya, Janeth I. Sanchez
Journal: Journal of Clinical Oncology (2022)

1587 Background: Researchers commonly use “Primary Payer at Diagnosis” measured in cancer registry data to assess the impact of health policy, such as the Affordable Care Act, on insurance, and the impact of insurance on cancer care and outcomes. Measurement error may bias estimated effect size and significance. Little is known about patterns of Medicaid or Medicare misreporting in registry databases commonly used for policy analysis. Methods: We used the National Cancer Institute’s Surveillance, Epidemiology and End Results registry data for adults aged 19-64 years at diagnosis with known cancer stage, linked to most recently available (2007-2011) CMS records on Medicaid and Medicare enrollment at diagnosis month. We recoded the registry Primary Payer variable into 6 categories: private/managed care, Medicare, Medicaid, other government, status unknown, uninsured. State-year policy data regarding Medicaid eligibility and managed care enrollment were also linked. We compared the registry data to Medicaid and/or Medicare enrollment data, and calculated underreporting rates by patient characteristics and state policy. Results: The linked sample (N = 896,031) was 68% non-Hispanic white, 49% male. Overall, the registry data reported 7.8% Medicare and 10.1% Medicaid, while enrollment was 5.5% Medicare, 10.4% Medicaid, and 3.4% dual Medicare-Medicaid. The registry data concordantly identified 61.4% and 57.7% of persons identified per enrollment data to be Medicaid-only and Medicare-only, respectively (Table). Most Medicaid-only enrollees without concordant registry information were reported to have private insurance or be uninsured. Medicaid underreporting (39% overall), was higher for males (43%) vs females (37%), in low (46%) vs high (38%) poverty areas, for Medicaid poverty expansion or waiver enrolled (50%) vs cash assistance related eligibility (33%), and in states with large managed care enrollment, all at p&lt;.001. If Medicaid and Medicare enrollment data were used to edit the registry data, 8% of persons would switch insurance assignment. Conclusions: Primary Payer data reported by cancer registries are subject to measurement error and may result in biased estimates of insurance-related policy impacts. Enhancement with objective Medicaid and Medicare enrollment data will reduce measurement error and may result in unbiased estimates necessary to support policy assessment. [Table: see text]
LINC-15. Sustaining multidisciplinary care of children with central nervous system tumors during the COVID-19 pandemic
Authors: Faustine Richelle Ong, Ronnie Baticulon, Ana Patricia Alcasabas
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: A multidisciplinary team (MDT) approach is essential for quality cancer care. Since 2019, we have conducted regular MDT meetings to discuss pediatric patients with central nervous system (CNS) tumors at the Philippine General Hospital. Because of COVID-19, an abrupt transition from in-person to virtual meetings became necessary. METHODS: We reviewed the proceedings of MDT meetings for pediatric CNS tumors from March 2020–December 2021. We identified the strategies and adaptations of our pediatric neuro-oncology group, and outlined recommendations for other institutions in low- and middle-income countries. RESULTS: Our pediatric neuro-oncology group conducted 18 virtual MDT meetings during the study period. Meetings were scheduled every last Tuesday of the month, with pediatric oncologists, neurologists, neurosurgeons, radiation oncologists, radiologists, and neuropathologists regularly attending. We invited other specialists as needed. In total, we had 135 case discussions for 79 unique patients, or about 8 patients per meeting. These included both inpatients (74%) and outpatients (26%). Ten patients received prior treatment elsewhere. At the time of the meeting, 86% were postoperative, 8% were preoperative, and 6% did not require surgery. Most (60%) had malignant CNS tumors and 15% had disseminated/leptomeningeal disease. Histopathologic diagnosis was obtained for 62 patients (79%). Concerns addressed were: formulating a treatment plan (88%), surveillance strategy (10%), and diagnostic workup (5%). DISCUSSION: Several factors contributed to the ease of online transition: (1) motivated care providers including a patient navigator, (2) fixed schedule, (3) institutional Zoom account for securing data privacy, and (4) availability of picture archiving and communication system (PACS) for neuroimaging. Challenges included: (1) delays due to internet connectivity, (2) Zoom fatigue and online distractions, and (3) risk for miscommunication or misunderstanding. Commitment of the entire neuro-oncology team is essential to ensure the delivery of best possible care for pediatric patients with CNS tumors.
QOL-07. The importance of an onco-fertility program for pediatric neuro-oncology patients
Authors: Irene IJgosse, Leendert Looijenga, Aart Klijn, Ralph Oude-Ophuis, Marry van den Heuvel, margreet Veening, Annelies Bos, Simone Broer, Jeanette van Leeuwen, Lideke van der Steeg, Marianne van de Wetering
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: In the Netherlands pediatric oncology care is centralized in one hospital since 2018. 600 new patients a year are seen with 100-120 new neuro-oncology (NO) patients. Of the NO patients 20-25% classify as high risk for infertility (HR) such as patients with medulloblastoma, ependymoma, ATRT and germinoma . An onco-fertility program was started navigated by a nurse-practitioner. The program runs with intense collaboration between the different specialties. All new patients are identified according to the international guidelines on fertility care. The fertility-risk is based on the CED score (cyclofosfamide equivalent dose) and radiotherapy dose. Since 2018 awareness was created by teaching sessions among colleagues, nursing staff, and parent association organizations. METHODS: All HR children are informed by the nurse-practitioner and can be referred for counseling to gynaecology for OTC (ovarian tissue cryopreservation) or urology for sperm cryopreservation or testicular biopsy. Monthly the onco-fertility working-group members discuss cases and research in the field. RESULTS: In 2019, 19% NO cases and in 2020 18% of cases were HR for infertility. In both years 36% of these cases had fertility preservation performed. In 2021, 22% cases HR were identified and in 55% preservation was performed. Reasons for not preserving fertility were diverse, varying from poor prognosis, or too ill to be included. CONCLUSION: Awareness of the fertility risk in NO patients who are HR is necessary. These patients need to be informed, and stratified for counseling and offered fertility preservation before start of their treatment. An active onco-fertility program helps to offer the best option for future fertility for these patients
Molecular profile of exosomal miRNA differential expression in ascites of untreated advanced gastric cancer patients with peritoneal metastases.
Authors: Yi Wu, Changsong QI, Jing Gao, Xiaoyi Chong, Lin Shen
Journal: Journal of Clinical Oncology (2022)

e16086 Background: The incidence of gastric cancer is high, and the proportion of peritoneal metastases among patients with early-stage operable gastric cancer is about 10%-20%, while the proportion of peritoneal metastases among patients with stage 3 (stage III) gastric cancer is as high as 40%. The prognosis of gastric cancer patients with peritoneal metastases is poor, with a median survival of 7 months. Exosomes are considered to be carriers of intercellular communication and abundant miRNAs (miRNAs) are enriched in patients' ascitic fluid exosomes. Methods: Ascites exosomes were characterized according to ISEV2018. The pro-tumor proliferation and metastatic ability of ascites exosomes in gastric cancer patients with peritoneal metastases was observed by small animal in vivo imaging. Six untreated ascites exosomes from gastric cancer patients with peritoneal metastases were selected for miRNA sequencing with five ascites exosomes from patients with benign disease to determine differentially expressed molecular profiles. The target mRNAs of selected miRNAs were predicted by miRhybrid, TargetScan database, and enriched in KEGG database for the function of target mRNAs. Results: Compared to ascites exosomes from patients with benign disease, or ascites exosomes removed from gastric cancer patients with peritoneal metastases, ascites exosomes from gastric cancer patients with peritoneal metastases had a significant contribution to tumor proliferation and metastasis. Among them, molecules such as miR-196 were expressed up-regulated in all six samples of gastric cancer peritoneal metastasis group, and the difference was significant. The target mRNAs of differentially expressed miRNAs were associated with motility, adhesion, stromal degradation, hypoxia tolerance, apoptosis, and angiogenesis (biological behaviors involved in this process of gastric cancer peritoneal metastasis). Conclusions: Molecules such as miR-196 are important for the clinical problem of peritoneal metastasis of gastric cancer and can be used as biomarkers for disease assessment and potential therapeutic target.
Phase 1/2a trial of nadunolimab, a first-in-class fully humanized monoclonal antibody against IL1RAP, in combination with cisplatin and gemcitabine (CG) in patients with non-small cell lung cancer (NSCLC).
Authors: Astrid Paulus, Saulius Cicenas, Zanete Zvirbule, Luis G. Paz-Ares, Ahmad Awada, Ignacio Garcia-Ribas, Nedjad Losic, Marius Zemaitis
Journal: Journal of Clinical Oncology (2022)

9020 Background: Interleukin-1 Receptor Accessory Protein (IL1RAP) is expressed by cancer and stromal cells of many solid tumors. The IL-1 pathway is active in tumors and upregulated in response to chemotherapy. IL1RAP interacts with IL-1R1 and modulates downstream factors (e.g. IL-6, IL-8) and CRP level. Nadunolimab (CAN04), a fully humanized ADCC-enhanced IgG1 antibody, targets IL1RAP and blocks IL-1α and IL-1β signaling. Here, results are reported from the phase 1/2a clinical trial CANFOUR evaluating nadunolimab combined with CG in NSCLC. Methods: Patients (pts) with unresectable, locally advanced or metastatic NSCLC, progressed on pembrolizumab or in first line for advanced disease, were eligible. Pts received 1 (n =17), 2.5 (n = 3) or 5 mg/kg (= 13) nadunolimab given Q1W in Cycle 1 and Q2W from Cycle 2, combined with standard CG. Due to risk of infusion-related reactions, a priming dose of 0.5 mg/kg nadunolimab was given one week before CG. Primary objective was safety; secondary objectives included ORR, PFS and OS, and exploratory objectives included effects on serum and tumor tissue biomarkers. Results: Thirty-three pts were enrolled: median age 64 years (39-77), 30% female, 42% ECOG 0, 55% non-squamous histology, 82% stage IV, 45% received previous pembrolizumab monotherapy. Treatment-related adverse events of grade≥3 were observed in 73% of pts, including neutropenia (58%), febrile neutropenia (9%), thrombocytopenia (30%) and anemia (18%). Neutropenia could be managed by G-CSF. Thirty pts received combination therapy and were included in the efficacy analysis. Three pts did not receive chemotherapy due to clinical deterioration (n = 2) or consent withdrawal (n = 1). ORR was 53% (95% CI 34-72%), disease control rate 80% (61-92%) and median duration of response 5.5 months (3.7-7.0) with 23% of pts still on treatment. The lower limit of the 95% CI for the observed ORR excludes the pre-specified 30%. ORR in pts with squamous histology was 46% and non-squamous 56%. Median PFS was 6.7 months (5.5-7.3) and median OS 13.7 months. The neutrophil-lymphocyte ratio was reduced throughout the trial and was driven by the reduction in circulating neutrophil numbers. IL1RAP expression on both cancer and stromal cells was confirmed in tumor biopsies. Conclusions: Nadunolimab combined with CG shows manageable safety and promising efficacy with a response rate of 53% in NSCLC pts. Nadunolimab is currently evaluated in several clinical trials investigating chemotherapy or IO combinations, including carboplatin and pemetrexed in non-squamous NSCLC. Clinical trial information: NCT03267316.
The role of lymph node dissection in patients undergoing salvage radical prostatectomy for radiation recurrent prostate cancer
Authors: F. Quhal, P. Rajwa, E. Laukhtina, H. Mostafai, B. Pradere, P. Gontero, R. Mathieu, A. Briganti, A. Heidenreich, S.F. Shariat
Journal: European Urology (2022)
Bioengineered 3D Tissue Model of Intestine Epithelium with Oxygen Gradients to Sustain Human Gut Microbiome
Authors: Ying Chen, Sara E. Rudolph, Brooke N. Longo, Fernanda Pace, Terrence T. Roh, Rebecca Condruti, Michelle Gee, Paula I. Watnick, David L. Kaplan
Journal: Advanced Healthcare Materials (2022)

Abstract The human gut microbiome is crucial to hosting physiology and health. Therefore, stable in vitro coculture of primary human intestinal cells with a microbiome community is essential for understanding intestinal disease progression and revealing novel therapeutic targets. Here, a three‐dimensional scaffold system is presented to regenerate an in vitro human intestinal epithelium that recapitulates many functional characteristics of the native small intestines. The epithelium, derived from human intestinal enteroids, contains mature intestinal epithelial cells and possesses selectively permeable barrier functions. Importantly, by properly positioning the scaffolds cultured under normal atmospheric conditions, two physiologically relevant oxygen gradients, a proximal‐to‐distal oxygen gradient along the gastrointestinal (GI) tract, and a radial oxygen gradient across the epithelium, are distinguished in the tissues when the lumens are faced up and down in cultures, respectively. Furthermore, the presence of the low oxygen gradients supported the coculture of intestinal epithelium along with a complex living commensal gut microbiome (including obligate anaerobes) to simulate temporal microbiome dynamics in the native human gut. This unique silk scaffold platform may enable the exploration of microbiota‐related mechanisms of disease pathogenesis and host‐pathogen dynamics in infectious diseases including the potential to explore the human microbiome‐gut‐brain axis and potential novel microbiome‐based therapeutics.
Multimodal integration of radiology, pathology, and genomics for prediction of response to PD-1 blockade in patients with non–small cell lung cancer.
Authors: Jia Luo, Rami S Vanguri, Andrew T Aukerman, Jacklynn V. Egger, Christopher J Fong, Natally Horvat, Andrew Pagano, Jose Araujo-Filho, Luke Geneslaw, Hira Rizvi, Ramon Sosa, Kevin Boehm, Soo-Ryum Yang, Katia Ventura, Travis Hollman, Michelle S. Ginsberg, JianJiong Gao, Matthew David Hellmann, Jennifer L. Sauter, Sohrab P Shah
Journal: Journal of Clinical Oncology (2022)

9064 Background: Immunotherapy is now given to almost all patients with advanced non-small cell lung cancer (NSCLC). However, developing robust biomarkers to predict benefit remains challenging. We set out to evaluate the predictive capacity of integrating medical imaging, histopathologic, and genomic features to develop a multimodal biomarker for immunotherapy response. Methods: We used baseline data that is routinely obtained during diagnostic clinical workup at a single center in patients with NSCLC and known outcomes following immunotherapy. The multimodal dataset included DNA alterations from NGS, CT scan images, and digitized PD-L1 immunohistochemistry (IHC) slides. Guided by experts in each field, we developed a workflow to extract data for each patient and used an attention-gated machine learning approach to integrate the features into a risk prediction model. Results: Our cohort included 247 patients with advanced NSCLC who received immunotherapy and had complete radiology, pathology, genomic, and clinical data. The patient cohort was 54% female, had a median age of 68 years (range 38-93), and 88% patients had a smoking history. Responders (CR/PR) vs non-responders (SD/PD) showed a median PFS and OS of 2.7 months (95% CI 2.5-3.0) and 11.4 months (95% CI 10.3-12.8), respectively. Of all patients, 187 (76%) had segmentable disease on chest CT scans. We used a radiomics approach and aggregated the average individual lesion predictions to construct patient-level response predictions which resulted in an overall AUC = 0.65, 95% CI 0.57-0.73. We next studied digitized FFPE slides of pre-treatment PD-L1 IHC staining of tumor specimens. Overall, 52% of slides showed PD-L1 tumor proportion score (TPS) ≥ 1% and were used to extract IHC-texture, a novel spatial characterization of PD-L1 staining. Logistic regression modeling on IHC-texture resulted in prediction accuracy of AUC = 0.62 (95% CI 0.51-0.73) which was inferior to the pathologist-assessed PD-L1 TPS (AUC = 0.73, 95% CI 0.65-0.81). We next implemented a dynamic deep attention-based multiple instance learning model with masking to evaluate the impact of combining features from all modalities. Our multimodal model (AUC = 0.80, 95% CI 0.74-0.86) outperformed unimodal measures, including tumor mutational burden (AUC = 0.61, 95% CI 0.52-0.70) and PD-L1 TPS (AUC = 0.73, 95% CI 0.65-0.81). Conclusions: Our study is a proof of concept for using multimodal features to improve prediction of immunotherapy response over standard-of-care approaches in patients with NSCLC using expert-guided machine learning.
Association of LAG-3 expression in circulating T cells and response to combination temozolomide (TMZ) and nivolumab (NIVO) in advanced neuroendocrine neoplasms (NENs): Results from an investigator-initiated phase 2 trial.
Authors: Vineeth Sukrithan, Brooke Benner, Lai Wei, Ashima Goyal, Ye Zhou, Sheryl-Ann Suffren, Carly Pilcher, Gwen Christenson, Nancy Curtis, Emily Schwarz, Himanshu Savardekar, Ruthann Norman, Barbara Kleiber, Robert Wesolowski, Gregory Alan Otterson, Claire F. Verschraegen, William Edgar Carson, Manisha H. Shah, Bhavana Konda, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2022)

4123 Background: LAG-3 is an immune checkpoint present on NK cells, activated T cells and myeloid cells that inhibit T cell responses. Recent evidence demonstrating the safety and efficacy of LAG-3 inhibition has increased interest in this pathway for the treatment of multiple malignancies but the role in NEN is unclear. We present results from correlative peripheral blood mass cytometry (CyTOF) performed in a phase 2 trial (NCT03728361) of the combination of NIVO and TMZ in pts with advanced NEN. Methods: Patients (pts) with progressive NEN of any grade or primary location and any line of therapy were eligible. Small cell lung cancer was excluded. Clinical results from NCT03728361 will be presented in a separate abstract. Study treatment consisted of NIVO 480 mg IV every 4 weeks and TMZ 150 mg/m2 for 5 consecutive days out of a 28-day cycle. Peripheral blood mononuclear cells (PBMCs) were available from 16 out of 28 patients at screening (baseline) and cycle 1, day 15 (C1D15) and analyzed via CyTOF. Antibody labelling was performed using a 37 marker Maxpar Direct Immune Profiling Assay (Fluidigm). Immune cell populations were compared using two sample t-tests between pts with partial response (PR) and non-partial response (non-PR). Results: At screening, no differences were observed in PD-1, TIM3, or KLRG1 positive T-cell populations between pts with PR or non-PR. Patients with a PR had a significantly lower % of LAG-3 expressing T cells (p=0.029). There was a trend towards a lower % CD8+LAG-3+ T cells in pts with PR (p=0.086). At C1D15: The % of CD8+ LAG-3+ T cells were significantly higher in PRs vs. non-PR (p = 0.015). In matched samples comparing T cell populations at screening to C1D15, LAG-3+ CD8+ T cells increased significantly in PRs when compared to non-PRs (p=0.021). Conclusions: The % of LAG-3+ T cell population at baseline associates with non-response to TMZ/NIVO in NENs. Among responders, there was a significant increase in CD8+ LAG-3+ T cells by Day 15 compared to baseline indicating a potential mechanism of immune escape and eventual resistance. Clinical trial information: NCT03728361. [Table: see text]
Primary analysis of a phase 2, open-label, multicenter trial of talimogene laherparepvec (T-VEC) plus pembrolizumab (pembro) for the treatment (Tx) of patients (pts) with advanced melanoma (MEL) who progressed on prior anti–PD-1 therapy: MASTERKEY-115.
Authors: Brian Gastman, Caroline Robert, Helen Gogas, Piotr Rutkowski, Georgina V. Long, Marya F. Chaney, Harshada Joshi, Yu-Lin Lin, Wendy Snyder, Jason Alan Chesney
Journal: Journal of Clinical Oncology (2022)

9518 Background: Despite advances in anti–PD-1–based Tx for MEL, an unmet need remains for immunotherapy failure in advanced metastatic or unresectable MEL. Also, there is a growing population of pts who received adjuvant anti–PD-1 and recurred; yet trials to address this population are lacking. Combination Tx with T-VEC, an oncolytic viral intratumoral Tx designed to produce GM-CSF, and pembro, an anti–PD-1 agent, may overcome immunotherapy failure. We report the MASTERKEY-115 primary analysis on the efficacy and safety of T-VEC + pembro in pts with advanced MEL who had progressive disease (PD) on prior anti–PD-1. Methods: This open-label, single-arm, multicenter, phase 2 study (NCT04068181) enrolled pts at 26 international sites (Jan 2020‒Feb 2021). Cohorts 1 and 2, primary and acquired resistance, respectively, received anti–PD-1 in a locally recurrent or metastatic setting and had PD within 12 wks of the last anti–PD-1 dose. Cohorts 3 and 4 included only pts who received adjuvant anti–PD-1 and were disease-free for &lt; 6 mos (Cohort 3) or ≥ 6 mos (Cohort 4) before confirmed PD. Eligible pts had histologically confirmed unresectable or metastatic stage IIIB–IVM1d MEL, measurable and injectable disease, ECOG PS 0/1, and progressed on anti–PD-1 directly before enrollment. T-VEC at standard dosage and pembro 200 mg were given Q3W. The primary endpoint was objective response rate (ORR). Key secondary endpoints were complete response (CR) rate, progression-free survival (PFS), and safety. Tx decisions were per modified immune-related response criteria (irRECIST). Results: 72 pts (median age, 65 y) were enrolled. Of the 71 evaluable pts, 37 (52.1%) had stage IVM1b‒d disease, 30 (42.3%) had confirmed PD-L1–positive tumor (CPS ≥ 1%), 20 (28.2%) had a BRAF V600 mutation, and 21 (29.6%) had LDH &gt; 1ULN. At data cutoff (Aug 2021), 47 (65.3%) pts remained on study. ORR was 0%, 6.7%, 40%, and 46.7% in cohorts 1–4, respectively (table). Any-grade Tx-related adverse events (TRAEs) were reported in 54 (76.1%) pts; the most common were pyrexia (29.6%), fatigue, and influenza-like illness (15.5% each). Grade ≥ 3 TRAEs occurred in 9 (12.7%) pts. Conclusions: T-VEC + pembro showed manageable safety in pts with advanced MEL after anti–PD-1 failure; the promising ORR observed in pts who progressed on prior adjuvant anti–PD-1 warrants further analysis. Clinical trial information: NCT04068181. [Table: see text]